UTSW Internal Medicine Journal Watch (March 2014) Table of Contents Infectious Diseases ............................................................................................................................... 2 Cardiology ................................................................................................................................................ 3 Nephrology .............................................................................................................................................. 3 General Internal Medicine ................................................................................................................. 4 Palliative Care ........................................................................................................................................ 4 Geriatrics .................................................................................................................................................. 5 Additional interesting reads based on specialty ....................................................................... 5 Hematology/Oncology ..................................................................................................................................... 5 1 Infectious Diseases 1. Lawitz E, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naïve and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomized, phase 2 trial. Lancet 2014 Feb 8; 383 (9916): 515-23. Commentary: This study highlights, along with others, that interferon-free treatment in a one pill once a day regimen for almost all patients with HCV is almost here. This will be a game-changer for the treatment of HCV if it can be applied widely. Despite small numbers in phase 2 trial that will need to be confirmed in large trials, this demonstrates a fixed-dose one pill interferon-free regimen with sustained virological response (SVR) rates > 95% regardless of previous treatment status or presence of cirrhosis. The combination will likely be available for clinical use in the next year. Link: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962121- 2/fulltext 2. Wunderink RG and Waterer GW. Community-Acquired Pneumonia. N Engl J Med 2014 Feb; 370:543-551. Commentary: Important review article of guidelines and new trends in CAP. Especially important is the emphasis on risk prediction for severity of disease and evidence supporting duration of Rx of 7 days or less in patient's with appropriate clinical response. However, the most important aspect is to highlight that current risk factors for so-called healthcare-associated PNA do not adequately predict risk for resistant bacteria and leads to overuse of broad-spectrum antibiotics. The concept of HCAP is likely to be revised or replaced in expected updated guidelines to come out in the next few years. Link: http://www.nejm.org/doi/full/10.1056/NEJMcp1214869 3. Visconti AJ, et al. Follow-up Imaging for Vertebral Osteomyelitis: A Teachable Moment. JAMA Intern Med 2014 Feb 1; 174(2):184. Commentary: Brief vignette that highlights cost-conscious and "Choosing Wisely" approach to avoiding unnecessary follow-up imaging in spinal osteomyelitis, which will often lag behind clinical improvement and confuse rather than clarify clinical decision making. Link: http://archinte.jamanetwork.com/article.aspx?articleid=1783048 2 4. HCV Guidelines Website Commentary: A joint effort of the AASLD and IDSA, this website is continuously updated and provides the latest guidelines on management and treatment of HCV in an era where the available drug treatments and clinical trial evidence is changing rapidly. Link: http://www.hcvguidelines.org/ Cardiology 1. 2014 AHA/ACC Valvular Heart Disease Guidelines Commentary: It is the first update in 6 years incorporating significant advancements. The highlights are as mentioned below a. 4 Stages of valve disease, similar to what we use for CHF— this is new nomenclature in the valve field b. Discussion about surgical risk scores (STS- Prom) and categories of patients who should be considered for intervention, and a new category for where surgical risk is prohibitive (>50% 1 year mortality, >= 3 organ systems compromised) c. Includes information on TAVR and when it should be considered d. Some modification to Aortic stenosis and mitral regurgitation where asymptomatic individuals can be offered surgery, even before LV dilation in the case of MR, now that operative risk has improved. Link: http://content.onlinejacc.org/article.aspx?articleid=1838843 Nephrology 1. Risk of End-StageRenal Disease Following Live Kidney Donation. JAMA. 2014 Commentary: This is an important article highlighting that inspite of the increased relative risk of ESRD for live kidney donors the absolute risk is very small if the donors are carefully selected. Link: http://jama.jamanetwork.com/article.aspx?articleid=1829682 3 General Internal Medicine 1. Grant, RW et call. Exercise as a Vital Sign: A Quasi-Experimental Analysis of a Health System Intervention to Collect Patient-Reported Exercise Levels. JGIM Vol 29, number 2, Feb 2014, p341-355. Commentary: This was an interesting study given a very simple intervention - just asking about exercise levels during nurse rooming as an additional 'vital sign' - lead to a small but significant improvement in not only documentation but also BMI and A1c's for diabetics. It reminds us that even just briefly talking to patients about self-management issues (obesity, smoking, etc) can help provide accountability and reinforce priorities which, over time (and with persistence), can make real differences. Link: http://link.springer.com/article/10.1007%2Fs11606-013-2693-9 Palliative Care 1. Wright AA, Zhang B, Keating NL, Weeks JC, Prigerson HG. Associations between palliative chemotherapy and adult cancer patients’ end of life care and place of death: prospective cohort study. BMJ 2014; 348:g1219. Commentary: An important study examining the importance of communicating clearly the risk and benefits of palliative chemotherapy in the terminally ill patients. Study included only those patients who had passed away. Patients receiving palliative chemotherapy at the time of enrollment were less likely to acknowledge that their illness was terminal, to report having discussed their end of life wishes with a physician and less likely to have completed a DNR order compared to those who were not. They were more likely to receive CPR, Mechanical ventilation during their last week and were likely to die in an ICU compared to those who weren’t on palliative chemotherapy. There was no significant difference in overall survival. However the results should be interpreted with caution since the study only included patients who had died (patient who had survived might have benefited). Nor should it be interpreted as meaning that the chemo should never be offered, since over 60% of respondents in the study said they would want chemotherapy even if it would only extend life by one week. Instead, the message should be that informed consent for palliative chemotherapy should include a full discussion of prognosis and goals of care. Dying in an ICU is not a bad thing if it represents fully informed consent and an exercise of autonomy, but it is to be avoided if instead it represents a failure of communication. Link: http://www.bmj.com/content/348/bmj.g1219 4 Geriatrics 1. Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease Link: http://www.nejm.org/doi/full/10.1056/NEJMoa1312889 2. Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease Link: http://www.nejm.org/doi/full/10.1056/NEJMoa1304839 3. Antiamyloid Therapy for Alzheimer's Disease — Are We on the Right Road? Link: http://www.nejm.org/doi/full/10.1056/NEJMe1313943 Commentary: The search for effective treatments for Alzheimer's disease has focused on targeting amyloid based on the amyloid hypothesis that deposition of amyloid in the brain is critical for the cascade of pathophysiologic changes responsible for developing dementia. The currently approved acetyl cholinesterase inhibitors have no effect on amyloid nor does the partial agonist/antagonist NMDA receptor Memantine. The development of antibodies that target amyloid was an exciting approach to prevent and treat the disease. However the results of these two phase 3 trials are disappointing and raise question about the role of amyloid and the amyloid hypothesis in the etiology of AD Additional interesting reads based on specialty Hematology/Oncology 1. Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV Link: http://www.nejm.org/doi/full/10.1056/NEJMoa1300662 2. How will B-cell-receptor–targeted therapies change future CLL therapy? Link: http://bloodjournal.hematologylibrary.org/content/123/10/1455.long 5 .